Interleukin-1beta and tumor necrosis factor-alpha are expressed by different subsets of microglia and macrophages after ischemic stroke in mice.
BACKGROUND
Interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) are expressed by microglia and infiltrating macrophages following ischemic stroke. Whereas IL-1beta is primarily neurotoxic in ischemic stroke, TNF-alpha may have neurotoxic and/or neuroprotective effects. We investigated whether IL-1beta and TNF-alpha are synthesized by overlapping or segregated populations of cells after ischemic stroke in mice.


METHODS
We used flow cytometry and immunohistochemistry to examine cellular co-expression of IL-1beta and TNF-alpha at 6, 12 and 24 hours after permanent middle cerebral artery occlusion in mice, validating the results by the use of bone marrow chimeric mice.


RESULTS
We found that IL-1beta and TNF-alpha were expressed in largely segregated populations of CD11b+CD45dim microglia and CD11b+CD45high macrophages, with cells expressing both cytokines only rarely. The number of Gr1+ granulocytes producing IL-1beta or TNF-alpha was very low, and we observed no IL-1beta- or TNF-alpha-expressing T cells or astrocytes.


CONCLUSIONS
Taken together, the results show that IL-1beta and TNF-alpha are produced by largely segregated populations of microglia and macrophages after ischemic stroke in mice. Our findings provide evidence of a functional diversity among different subsets of microglia and macrophages that is potentially relevant to future design of anti-inflammatory therapies in stroke.
Clausen
Bettina H
BH
Medical Biotechnology Center, University of Southern Denmark, Odense, Denmark. bclausen@health.sdu.dk
Lambertsen
Kate L
KL
Babcock
Alicia A
AA
Holm
Thomas H
TH
Dagnaes-Hansen
Frederik
F
Finsen
Bente
B
D000818:Animals; D002545:Brain Ischemia / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D018845:CD11 Antigens / Q000276:immunology; D019070:Cell Lineage / Q000276:immunology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004660:Encephalitis / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D005434:Flow Cytometry; D007150:Immunohistochemistry; D020244:Infarction, Middle Cerebral Artery / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D053583:Interleukin-1beta / Q000378:metabolism*; D017493:Leukocyte Common Antigens / Q000276:immunology; D008264:Macrophages / Q000145:classification / Q000276:immunology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D017628:Microglia / Q000145:classification / Q000276:immunology*; D020521:Stroke / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D018183:Transplantation Chimera; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D018845:CD11 Antigens; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D017493:Leukocyte Common Antigens; C516770:Ptprc protein, mouse